Various adhesive compositions were suggested in the last thirty years to replace the conventional metal assisted osteosynthesis method which uses various devices such as screws, plates and nails, in the treatment of fractures. Such compositions may offer a number of advantages over the conventional method such as bonding of particular fractures, ease and speed of fixation of fractures, excessive stiffness of current metal plates while providing a rigid fixation, etc.
Adhesive compositions to be useful for biomedical applications should respond to a quite large number of criteria such as:
to be inert; PA1 to be non-toxic by itself or by its degradation products; PA1 to be absorbed within the specific time of healing of the tissues that it binds; PA1 to allow the adjacent tissues to grow and unite through the adhesive barrier; PA1 to form a strong enough union which provides a uniform distribution of stresses over the entire applied area; PA1 to adhere quickly to moist tissues at body temperature; PA1 to be easily sterilizable, and PA1 to be economically satisfactory. PA1 The constituents of the compositions possess adequate shelf life at ambient conditions. PA1 They can be produced easily in large scale. PA1 They are able to be sterilized by recognized methods. PA1 They can be packaged in a form allowing antiseptic handling and transfer. PA1 Their initial setting time is reasonable without affecting the normal time of surgery.
to be non-carcinogenic and non-allergenic at long and short term;
In the use of adhesives for biomedical applications, there are also other factors apart from the immediate bonding. Thus for instance, chemical interference by moisture (blood), or fat (lipids) can change the surface properties of adherents and will affect the wettability. Also, the changing nature of the substrate may give rise to different initial exothermic chemical reactions during the formation of the adhesive joint.
In the past few decades there have been several studies on the bonding strength between bone and different adhesives such as epoxy resins, polyurethanes, polyacrylates, polymethacrylates and composite resins used in dentistry. A brief review of some specific prior references is hereafter presented.
Polyurethanes were extensively investigated about thirty years ago as adhesive reagents for bones. However, it was concluded that their use was not satisfactory for this application [G. Meyer et al, Biomat.Med.Dev.Art Org. 7(1), 55-71, 1979].
Alkyl-2-cyanoacrylates were also suggested and found to polymerize quite rapidly when applied to dry tissue surfaces. However, due to the exothermic polymerization and toxic degradation products, necrosis of surrounding tissue has been observed. Furthermore, it was found that these adhesives formed an impenetrable barrier between adjacent tissues thus interrupting the natural healing processes until biodegradation was accomplished.
In a very recent paper (J. Kilpikari et al, J. of Biomedical Materials Research, 20, 1095-1102, 1986) there are reported results on the bonding strength of alkyl-2-cyanoacrylates to bone in vitro. Although initially, the strength was quite high, it decreased after three weeks. According to the U.K. Patent No. 1,489,163 adhesive compositions for soft body tissues are suggested, being prepared from an aromatic diisocyanate, a macrodiisocyanate of a particular formula and 2,4,6-tris-(dimethylaminomethyl)phenol. Such adhesives are mentioned that were tested for effectiveness in the gluing of soft tissues of animal, in plastic repair of aponeurosis of the anterior abdominal wall and for reinforcing a cerebral aneurysm. A highly elastic porous polymeric film was formed on the vessel surface.
According to the European patent application No. 244,688 there are provided adhesive formulations for biomedical applications comprising: (a) a polyphenolic protein component of a specific decapeptide formula; (b) a cross-linking agent for the decapeptide; (c) a surfactant functioning as a spreading agent, and (d) a filler compatible with the intended use. Preferred surfactants which are suggested are sodium dodecylsulfate and sodium-dodecylsulfonate. The ratios between the above components depend according to the specific use intended for said compositions, e.g. biomedical adhesive in orthopedic repairs, ophthalmic adhesive for healing perforations, attachement of lenses or corneal components parts, dental adhesive to hold crown in place, medical adhesive for attachement of soft tissues, etc.
According to U.S. Pat. No. 4,740,534 surgical flexible adhesive with improved elasticity are obtained by a reaction betwen at least one NCO-terminated hydrophilic urethane, derived from a polyisocyanate and a polyol, and at least one unsaturated cyanoacrylate compound containing a cyano group attached to a carbon atom constituting the polymerizable double bond. The results submitted in the patent show that very fast curing times are achieved, but nothing is mentioned therein regarding the strength of the bonding which was obtained. The adhesives are supposed to be particularly useful for tisues such as blood vessels, heart, lung, esophagus, stomach, skin and the like.
The above brief review illustrates the long felt want for obtaining biomedical adhesive compositions for soft and calcified tissues which could be able to replace the conventional metal osteosynthesis devices.
It is an object of the present invention to provide new biomedical adhesive compositions for calcified tissues. It is another object of the present invention to provide new biomedical adhesive compositions for calcified tissues which are biocompatible and biodegradable. It is a further object of the present invention to provide new biomedical adhesive compositions which provide adequate tensile strengths during the time of healing of the treated fracture. It is yet another object of the present invention to provide biomedical adhesive compositions which are not interfering with the natural healing proccess of the injured bone.